Drug Interaction Report

CONTRAINDICATED: Coadministration with bictegravir may increase the plasma concentrations of dofetilide. The proposed mechanism is inhibition of organic cation transporter 2 (OCT2) and multidrug and toxin extrusion transporter 1 (MATE1) by bictegravir, resulting in decreased renal tubular secretion of dofetilide. Clinically, high plasma levels of dofetilide may increase the risk of QT interval prolongation, which has been associated with ventricular arrhythmias including torsade de pointes and sudden death.

MANAGEMENT: Given the risk for serious and/or life-threatening cardiovascular events associated with increased dofetilide plasma levels, concomitant use with bictegravir is considered contraindicated.

In vitro data suggest that grapefruit juice may inhibit the CYP450 3A4 first-pass metabolism of dofetilide. Decreased first-pass metabolism may increase dofetilide concentrations and increase the risk of QT interval prolongation and arrhythmias. The clinical significance is unknown, since dofetilide has a high oral bioavailability and a low affinity for CYP450 3A4. The manufacturer recommends caution.

Food enhances the oral absorption and bioavailability of tenofovir, the active entity of tenofovir disoproxil fumarate. According to the product labeling, administration of the drug following a high-fat meal increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of tenofovir by approximately 14% and 40%, respectively, compared to administration in the fasting state. However, administration with a light meal did not significantly affect the pharmacokinetics of tenofovir compared to administration in the fasting state. Food delays the time to reach tenofovir Cmax by approximately 1 hour. Tenofovir disoproxil fumarate may be administered without regard to meals.